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[Unilateral sacroiliitis in multiorgan tuberculosis].

A tight but painless soft-tissue swelling in the left parasternal region, with chronic cough and lumbo-ischial pain becoming progressively more severe over several months, occurred in a 27-year-old man. The chest X-ray film was normal, radiography of the iliosacral joints revealed right-sided sacroiliitis. In the further course of the illness night sweat, nightly fever up to 38 degrees C and weight loss of 7 kg in two months, as well as severe treatment-resistant earache developed. When hospitalized, another chest X-ray film showed disseminated small nodular foci pointing to tuberculosis. Sputum and irrigation fluid from the right middle-ear contained Mycobacterium tuberculosis. Biopsy material from the parasternal tumour and middle-ear mucosa contained caseous granulomas, confirming the diagnosis of tuberculous sacroiliitis as part of multi-organ tuberculosis. Tuberculostatic treatment--400 mg isoniazid, 600 mg rifampicin, and 1,500 mg pyrazinamide daily (the latter discontinued after 8 weeks)--normalized the appearance in the chest X-ray film. The patient returned to his home in Holland and, four years later, reported that he was free of any symptoms, even during sport activity.

Adult↗

[The manifestations of extrapulmonary tuberculosis].

Seven weeks after a generalized cerebral seizure a 27-year-old woman from Ghana developed nausea, vomiting and weight loss, gradually increasing over two weeks. Cranial computed tomography revealed several hyperdense formations with extensive associated oedema and a midline shift. Among extensive biochemical tests only a raised erythrocyte sedimentation rate of 24/50 mm and leukopenia of 2,600/microliters (with normal differential count) were notable. Diagnostic laparotomy was performed because of sonographic and computed tomographic evidence of enlarged abdominal lymph nodes. Histological examination of representative lymph nodes and of tiny nodules deposited on the peritoneum revealed caseous granulomatous inflammation. Mycobacterium tuberculosis was cultured from these specimens. Antituberculosis treatment was started with 0.3 g/d isoniazid, 0.6 g/d rifampicin, 2 g/d pyrazinamide and 1 g/d streptomycin, plus dexamethasone, 4 mg four times daily. After eight weeks treatment an intracerebral focus, removed to exclude neoplasm, proved histologically to be a tuberculoma. Only after four months was it possible to reduce the glucocorticoid dosage to prednisone, 20 mg/d. The antituberculosis treatment was continued for 18 months, with only isoniazid and rifampicin taken during the last 14 months. Final clinical and biochemical examinations were unremarkable. Computed tomography demonstrated regression of the abdominal lymph nodes and the cerebral foci. The patient was without any symptoms.

Adult↗

[Hypercalcemia in florid pulmonary and cervical lymph node tuberculosis].

A 57-year-old man with a history of tuberculosis (TB of the knee-joint 44 years ago and open pulmonary TB six months ago with poor patient drug compliance) had lost 10 kg in weight during the preceding six months. In addition, firm lymph-node swellings with redness of the overlying skin and a skin fistula developed on the right side of the neck. There was mild hypercalcaemia (albumin-corrected serum calcium concentration 2.59 mmol/l) and hyperphosphataemia (2.0 mmol/l) with low-normal serum concentrations of parathormone and of 25-hydroxy-vitamin D3 (14 ng/ml). Serum 1,25-dihydroxy-vitamin D3 concentration was reduced (16 ng/l). The activity of osseous isoenzyme of alkaline phosphatase was normal (19 U/l) and skeletal scintigraphy revealed no abnormality. The cervical lymph-nodes were excised (histology: active caseous lymph-node TB). Tuberculostatic treatment was begun with daily doses of 0.3 g isoniazid, 0.45 g rifampicin, 1.2 g ethambutol and 1.5 g pyrazinamide. Serum calcium concentration rose to 3.22 mmol/l (albumin-corrected) in the first two weeks, even though the patient was on a low-calcium diet. The various concentrations subsequently decreased, but remained slightly elevated throughout the period of observation (11 weeks). This is thus a case of TB-associated hypercalcaemia which was not caused by 1,25-dihydroxy-vitamin D3 or bone destruction.

Alcoholism↗

[Involvement of the central nervous system in disseminated tuberculosis].

Four weeks after starting tuberculostatic treatment (with isoniazid, rifampicin, streptomycin and pyrazinamide) a 21-year-old man with pulmonary tuberculosis developed symptoms of a radiculomyelopathy as well as mild renal failure. After isoniazid and streptomycin had been discontinued and ethambutol and high doses of vitamin B6 had been added all signs and symptoms improved. However, 4 weeks later tuberculous meningitis occurred which at first seemed to respond to administration of 5 antituberculosis drugs and dexamethasone. But 3 weeks later the patient sustained a partial hemiparesis. Its cause was proven to be a tuberculoma in the region of the brainstem. During further administration of tuberculostatic drugs and glucocorticoids the symptoms gradually receded over 8 months. A 54-year-old man with pulmonary tuberculosis developed cranial nerve pareses and symptoms of cerebellar involvement (trunk ataxia, intention tremor, dysdiadochokinesia) 3 weeks after starting tuberculostatic treatment. Computed tomography revealed multiple intracerebral tuberculomas which gradually shrank with continuation of the tuberculostatic treatment plus glucocorticoids. These two case reports illustrate that in tuberculosis involvement of the CNS can express itself clinically through complex symptoms, sometimes even after the start of tuberculostatic treatment.

Adrenal Cortex Hormones↗

Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months.

BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.

AIDS-Related Opportunistic Infections↗

Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.

Adult↗

Mycobacterium of an unknown strain causing a primary tumoral process of the orbital roof.

PURPOSE. To report an unidentified species of atypical Mycobacterium as the causative agent of a primary orbital roof infection. METHOD. Review of a case from the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. RESULTS. The patient had a negative history for eye trauma. Computed tomography (CT) of the brain and right orbit confirmed the presence of soft tissue swelling and erosive changes in the orbital roof bone, with intact globe and external ocular muscles. Biopsy of the lesion showed non-caseating, granulomatous osteomyelitis. Various stains of the sample were negative. Since our institution could not identify the causative organism, a biopsy sample was sent to Bioscientia Laboratory in Germany; the culture grew an atypical Mycobacterium of unknown species. Their sensitivity study showed the organism to be resistant to pyrazinamide, isoniazide and streptomycin, but sensitive to rifampicin, ethambutol, and prothionamide. Systemic checkup and investigation ruled out any other systemic involvement. CONCLUSION. A new species of atypical Mycobacterium was recovered from a primary orbital infection. The infection responded to combined antituberculous therapy.

Journal Article↗

Let's stop the comeback of tuberculosis. Best drug regimens for prevention and treatment.

Tuberculosis has been on the increase in recent years, so physicians need to be aware of it once again. Very effective drugs are available to treat the disease. Pharmacokinetics, dosing schedule, and adverse reactions of each anti-tuberculous agent need to be considered. A short (6-month) course of therapy is now recommended: Isoniazid, rifampin (Rifadin, Rimactane), and pyrazinamide are given for the initial 2 months, followed by isoniazid and rifampin for 4 months. If drug resistance is a factor, a fourth drug is added to the initial regimen, and therapy may have to be extended. Chemoprophylaxis with isoniazid is very important to reduce the incidence of tuberculosis. It should be given to all high-risk persons.

Antitubercular Agents↗

Tuberculosis.

Tuberculosis is caused by Mycobacterium tuberculosis, transmitted primarily by inhalation of aerosolized droplets containing the organisms. There is an infection of the respiratory tract and the tubercle bacilli spread via lymphatic system and bloodstream to many different organs. Generally, the pulmonary tuberculosis infections are asymptomatic and a positive skin test result is the only indication of it. Approximately 10% of infected individuals develop active disease. Immunosuppression caused by systemic diseases or medication increases the risk of developing tuberculosis. In addition to the pulmonary tract, tuberculosis may affect many organs and systems, including lymph nodes, larynge, middle ear, genitourinary tract, musculoskeletal system, central nervous system, gastrointestinal tract, pericardium, and skin. Ocular involvement is an uncommon event in tuberculous infection, and there are several presentations involving the iris, ciliary body, choroid, retina and optic nerve. The diagnosis is based in the detection of mycobacteria in fluids and tissues. If there is no available material for analysis, a presumptive diagnosis is made and therapeutic test initiated. The therapy is based in anti-tuberculous drugs and corticosteroids. The standard treatment protocol in Brazil includes isoniazid, rifampim, and pyrazinamid for two months, followed by isoniazid and rifampin for four months for susceptible organisms. Alternative regimens are necessary in the presence of drug resistance.

Antibiotics, Antitubercular↗

Tuberculosis verrucosa cutis in a patient with long-standing generalized lichen planus: improvement of lichen after antitubercular polychemotherapy.

Tuberculosis verrucosa cutis (TBVC) is a rare form of skin tuberculosis in Western communities, and is generally seen in certain risk groups. A 52-year-old housewife with recalcitrant generalized cutaneous and mucosal lichen planus (LP) of more than a 20-year duration presented with an erythematous-edematous plaque with a warty surface containing deep hemorrhagic fissures and numerous orifices draining purulent material on the back of her left hand. On the basis of clinical, histological and bacteriological findings, TBVC was diagnosed. The patient was successfully treated with isoniazid, rifampicin, ethambutol and pyrazinamide. Interestingly, all lichen lesions improved completely with this therapy. To the best of our knowledge, this is the first documented case of TBVC associated with LP, which was cured by antitubercular polychemotherapy. The case is presented because it reflects a possible reciprocal causal relationship between two cutaneous conditions of different natures.

Antitubercular Agents↗

Urate homeostasis in polycystic kidney disease: comparison with chronic glomerulonephritic kidney.

Autosomal dominant polycystic kidney disease (ADPKD) might affect urate homeostasis and clearance. Renal tubular urate transport was studied by means of probenecid (PB) and pyrazinamide (PZA) tests in individuals with ADPKD and normal renal function as well as various degrees of renal failure (49 patients). Comparisons were made between polycystic and chronic glomerulonephritic kidney (CGNK), as well as with controls (men with normal renal function). Patients with ADPKD and normal renal function showed plasma urate levels within normal range and normal renal urate handling. In contrast higher plasma urate levels comparing to controls were found in patients with CGNK and normal renal function. During the evolution of renal failure ADPKD patients showed lower urate plasma levels and higher renal clearance as well as, fractional urate excretion, comparing to CGNK patients with the same degree of renal failure. In conclusion patients with ADPKD and normal renal function have normal urate handling and plasma urate levels within normal range. With increasing severity of disease and during evolution of renal failure CGNK patients showed higher urate plasma levels and lower clearances comparing to ADPKD patients. When renal disease becomes more advanced there was no difference in renal urate handling between ADPKD and CGNK patients.

Chronic Disease↗

Encephalopathy caused by isoniazid in a patient with end stage renal disease with extrapulmonary tuberculosis.

Tuberculosis infection is common in patients on maintenance hemodialysis, and the extrapulmonary presentations, which is usually asymptomatic, and only mild clinical presentation, are not uncommon. These hemodialysis patients were always prescribed multiple antituberculosis agents, including isoniazid, rifampin, ethambutol, and pyrazinamide, alongside their usual medication. Conscious disturbance was also frequently observed in these patients, with different paramount etiologies in the pre- and post-hemodialysis phases. We report a case undergoing maintenance hemodialysis, showing disturbed consciousness ten days following antituberculosis treatment for his established extrapulmonary tuberculosis infection. Consciousness was regained seven days later, after discontinuation of isoniazid.

Antitubercular Agents↗

Treatment of latent tuberculosis infection: renewed opportunity for tuberculosis control.

New recommendations for targeted tuberculin testing and treatment of latent tuberculosis (TB) infection have recently been published. Changes in nomenclature from screening to targeted tuberculin testing and from preventive therapy to treatment of latent TB infection (LTBI) are intended to promote more widespread implementation by programs and health care providers. Targeted tuberculin testing is designed to identify persons at high risk for TB and is discouraged for persons at low risk. New recommendations for treatment of LTBI in both human immunodeficiency virus (HIV)-infected and HIV-uninfected patients include isoniazid for 9 months as the preferred regimen: isoniazid for 6 months based on local program conditions, rifampin and pyrazinamide for 2 months, and rifampin for 4 months. Treatment monitoring now places greater emphasis on clinical, rather than routine, laboratory monitoring. More widespread implementation of targeted tuberculin testing and treatment of LTBI is an important control strategy that will enhance efforts to eliminate TB in the United States.

Antibiotics, Antitubercular↗

Issues in the treatment of active tuberculosis in human immunodeficiency virus-infected patients.

Most HIV-infected patients with tuberculosis can be treated satisfactorily with standard regimens with expectations of good results. Treatment of tuberculosis in these patients has been complicated by the introduction of HAART, which relies on drugs that interfere with the most potent class of antituberculous medications. Rifampin-free regimens or regimens that employ rifabutin may be acceptable strategies for patients who are receiving protease inhibitors, although these regimens have not been rigorously evaluated in patients with AIDS. At present, there is good reason to believe that a 6-month course of a rifabutin-containing regimen or a 9-12-month course of a regimen of streptomycin, isoniazid, and pyrazinamide should be adequate therapy for most patients with drug-susceptible disease. As the treatment of HIV infection with antiretroviral agents evolves, the treatment of tuberculosis in patients with AIDS is likely to evolve as well. This will require careful coordination of antituberculosis and antiretroviral therapies.

AIDS-Related Opportunistic Infections↗

Outcome of multidrug-resistant tuberculosis in human immunodeficiency virus-infected patients.

Among 324 cases of culture-proven tuberculosis from 1988 to 1996 in a hospital in Milan, Italy, 90 (27.8%) were due to Mycobacterium tuberculosis strains resistant to isoniazid and rifampin. Sixty-one of 69 isolates tested had identical restriction fragment length polymorphism patterns. The prevalent strain tested susceptible only to ethionamide and was also resistant to ethambutol, streptomycin, cycloserine, amikacin, kanamycin, terizodone, ofloxacin, rifabutin, rifapentin, and KRM 1648. The median survival time was 94 days. Multivariate analysis showed a trend toward better outcome in the period 1994-1996 (hazard ratio, 4.16; P<.001), and extrapulmonary localization of tuberculosis was the only other independent predictor of a negative outcome (hazard ratio, 2.1; P = .019). The delay from symptoms to beginning of therapy did not seem to be a determining factor in survival time. Standard antituberculosis therapy with four drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) had a higher efficacy than did other regimens with fewer drugs but without a statistically significant difference.

AIDS-Related Opportunistic Infections↗

Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats.

Moringa oleifera Lam (Moringaceae), commonly known as "Drumstick," is used in Indian folk medicine for the treatment of various illness. We have evaluated the hepatoprotective effect of an ethanolic extract of M. oleifera leaves on liver damage induced by antitubercular drugs such as isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA) in rats. Oral administration of the extract showed a significant protective action made evident by its effect on the levels of glutamic oxaloacetic transaminase (aspartate aminotransferase), glutamic pyruvic transaminase (alanine aminotransferase), alkaline phosphatase, and bilirubin in the serum; lipids, and lipid peroxidation levels in liver. This observation was supplemented by histopathological examination of liver sections. The results of this study showed that treatment with M. oleifera extracts or silymarin (as a reference) appears to enhance the recovery from hepatic damage induced by antitubercular drugs.

Alanine Transaminase↗

Antioxidant action of Moringa oleifera Lam. (drumstick) against antitubercular drugs induced lipid peroxidation in rats.

The protective effect of Moringa oleifera Lam. (Moringaceae) on hepatic marker enzymes, lipid peroxidation, and antioxidants was investigated during antitubercular drug (isoniazid, rifampicin, and pyrazinamide)-induced toxicity in rats. Enhanced hepatic marker enzymes and lipid peroxidation of antitubercular drug treatment was accompanied by a significant decrease in the levels of vitamin C, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase. Administration of Moringa oleifera extract and silymarin significantly decreased hepatic marker enzymes and lipid peroxidation with a simultaneous increase in the level of antioxidants. We speculate that Moringa oleifera extract exerts its protective effects by decreasing liver lipid peroxides and enhancing antioxidants.

Animals↗

Activity of 16 antimicrobial agents against drug-resistant strains of Mycobacterium tuberculosis.

The in vitro activity of 16 antimicrobial agents against 46 drug-resistant strains of Mycobacterium tuberculosis recently isolated from Italian patients was determined. As for first-line antituberculosis drugs, while isoniazid was ineffective against all the strains tested, resistance to streptomycin, rifampicin, pyrazinamide, and ethambutol was 80.4%, 71.7%, 39.1%, and 8.7%, respectively. Among second-line antituberculous drugs, resistance to ciprofloxacin, ofloxacin, and sparfloxacin and to amikacin and kanamycin was around 20%. About 10% of the strains were resistant to capreomycin and cycloserine and 4.3% were resistant to ethionamide; no strain was found to be resistant to thiacetazone, para-aminosalicylic acid, and viomycin. Although all strains displayed a rather continuous distribution of minimal inhibitory concentrations (MICs), a bimodal distribution was observed for rifampicin, amikacin, and kanamicin, with very high MIC values for resistant strains; relatively low MICs were found for fluoroquinolone-resistant strains. Among the small number of strains resistant to second-line agents, low resistant levels were observed. Restriction fragment length polymorphism analysis showed few strain clusters with resistance to first-line antituberculous drugs and aminoglycosides, fluoroquinolones, or both. Altogether, these results showed that second-line agents were still active against the isoniazid-resistant and multiply first-line resistant strains tested, with none or low resistance levels; these observations can be of importance for the treatment of multidrug-resistant tuberculosis in Italy.

Antitubercular Agents↗